Stabilnost kompleksa nekih lantanida s derivatima kumarina. II. Neodimij(III)-acenokumarol

A complex of neodymium(III) with 4-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one (acenocoumarol) was synthesized by mixing water solutions of neodymium(III) nitrate and the ligand (metal to ligand molar ratio of 1:3). The complex was characterized and identified by elemental analysis, conductivity, IR, 1H NMR and mass spectral data. DTA and TGA were applied to study the composition of the compound. Elemental and mass spectral analysis of the complex indicated the formation of a compound of the composition NdR3x6H2O, where R = C19H14NO6-. The reaction of neodymium(III) with 4-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one was studied in detail by the spectrophotometric method. The stepwise formation of three complexes, vis., NdR2+, NdR2+ and NdR3 was established in the pH region studied (pH 3.0-7.5). The equilibrium constants for 1:1, 1:2 and 1:3 complexes were determined to be log K1 = 6.20 ± 0.06; log K2 = 3.46 ± 0.07 and log K3 = 2.58 ± 0.05, respectively.Neodimijev(III) kompleks s acenokumarolom pripravljen je mješajući vodenu otopinu neodimijevog(III) nitrata i liganda u molarnom omjeru metala i liganda 1:3. Kompleks je karakteriziran i identificiran elementarnom analizom, konduktometrijom, IR, 1H NMR, masenom spektroskopijom, DTA i TGA. Analize ukazuju na sastav kompleksa NdR3.6H2O, gdje je R = C19H14NO6-. Reakcija neodimij(III) s acenokumarolom praćena je spektrofotometrijski. U pH području 3,0 do 7,5 utvrđeno je postupno stvaranje triju kompleksa, NdR2+, NdR2+ i NdR3. Konstante ravnoteže za 1:1, 1:2 i 1:3 komplekse bile su log K1 = 6,20 0,06, log K2 = 3,46 0,07, odnosno log K3 = 2,58 0,05

Stabilnost kompleksa nekih lantanida s derivatima kumarina. I. Cerijev(III)-4-metil-7-hidroksikumarin

A complex of cerium(III) with 4-methyl-7-hydroxycoumarin was synthesized by mixing water solutions of cerium(III) nitrate and 4-methyl-7-hydroxycoumarin sodium salt in a metal-to-ligand molar ratio of 1:2. The complex was characterized and identified by elemental analysis, conductometry, IR, 1H and 13C NMR-spectroscopy, mass spectral data, DTA and TGA. Thermal analysis of the complex indicated the formation of a compound of the composition Ce(R)2.(OH).5H2O, R standing for the ligand. The reaction of cerium(III) with 4-methyl-7-hydroxycoumarin was studied in detail by spectrophotometric method. The stepwise formation of two complexes, vis., CeR2+ and CeR2+, was established in the pH region studied. The equilibrium constants for 1:1 and 1:2 complexes were determined to be 10.72 and 9.22, respectively.Kompleks cerijevog(III) iona s 4-metil-7-hidroksikumarinom priređen je mješanjem vodene otopine cerijevog(III) nitrata i 4-metil-7-hidroksikumarin natrija u moalrnom omjeru 1:2. Kompleks je karakteriziran i identificiran elementarnom analizom, konduktometrijski, IR, 1H i 13C NMR-spektroskopijom, DTA, TGA i spektrometrijom masa. Termičkom analizom utvrđen je sastav kompleksa kao Ce(R)2.(OH).5H2O. Reakcija cerijevog(III) iona s 4-metil-7-hidroksikumarinom praćena je spektrofotometrijski. U proučavanom pH području utvrđeno je stupnjevito nastajanje dva kompleksa, CeR2+ i CeR2+. Konstante ravnoteže za 1:1 i 1:2 komplekse bile su 10,72, odnosno 9,22

Biomarker Exploration in Human Peripheral Blood Mononuclear Cells for Monitoring Sulforaphane Treatment Responses in Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is one of the most common neurodevelopmental disorders with no drugs treating the core symptoms and no validated biomarkers for clinical use. The multi-functional phytochemical sulforaphane affects many of the biochemical abnormalities associated with ASD. We investigated potential molecular markers from three ASD-associated physiological pathways that can be affected by sulforaphane: redox metabolism/oxidative stress; heat shock response; and immune dysregulation/inflammation, in peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with ASD. We first analyzed the mRNA levels of selected molecular markers in response to sulforaphane ex vivo treatment in PBMCs from healthy donors by real-time quantitative PCR. All of the tested markers showed quantifiability, accuracy and reproducibility. We then compared the expression levels of those markers in PBMCs taken from ASD patients in response to orally-delivered sulforaphane. The mRNA levels of cytoprotective enzymes (NQO1, HO-1, AKR1C1), and heat shock proteins (HSP27 and HSP70), increased. Conversely, mRNA levels of pro-inflammatory markers (IL-6, IL-1beta, COX-2 and TNF-alpha) decreased. Individually none is sufficiently specific or sensitive, but when grouped by function as two panels, these biomarkers show promise for monitoring pharmacodynamic responses to sulforaphane in both healthy and autistic humans, and providing guidance for biomedical interventions

Loss of Nrf2 abrogates the protective effect of Keap1 down regulation in a preclinical model of cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinomas (cSCC) are the most common and highly mutated human malignancies, challenging identification of driver mutations and targeted therapies. Transcription factor NF-E2 p45-related factor 2 (Nrf2) orchestrates a cytoprotective inducible program, which counteracts the damaging effects of solar UV radiation, the main etiological factor in cSCC development. Downregulation of Kelch-like ECH-associated protein 1 (Keap1), a Cullin-3/Rbx1 ubiquitin ligase substrate adaptor protein, which mediates the ubiquitination and proteasomal degradation of Nrf2, has a strong protective effect in a preclinical model of cSCC. However, in addition to Nrf2, Keap1 affects ubiquitination of other proteins in the carcinogenesis process, including proteins involved in inflammation and DNA damage repair. Here, we generated Keap1(flox/flox) SKH-1 hairless mice in which Nrf2 is disrupted (Keap1(flox/flox)/Nrf2(−/−)) and subjected them chronically to solar-simulated UV radiation. We found that the incidence, multiplicity and burden of cSCC that form in Keap1(flox/flox)/Nrf2(−/−) mice are much greater than in their Keap1(flox/flox)/Nrf2(+/+) counterparts, establishing Nrf2 activation as the protection mediator. Our findings further imply that inhibition of Nrf2 globally, a strategy proposed for cancer treatment, is unlikely to be beneficial

Of macrophages and red blood cells; a complex love story

Macrophages tightly control the production and clearance of red blood cells (RBC). During steady state hematopoiesis, approximately 10(10) RBC are produced per hour within erythroblastic islands in humans. In these erythroblastic islands, resident bone marrow macrophages provide erythroblasts with interactions that are essential for erythroid development. New evidence suggests that not only under homeostasis but also under stress conditions, macrophages play an important role in promoting erythropoiesis. Once RBC have matured, these cells remain in circulation for about 120 days. At the end of their life span, RBC are cleared by macrophages residing in the spleen and the liver. Current theories about the removal of senescent RBC and the essential role of macrophages will be discussed as well as the role of macrophages in facilitating the removal of damaged cellular content from the RBC. In this review we will provide an overview on the role of macrophages in the regulation of RBC production, maintenance and clearance. In addition, we will discuss the interactions between these two cell types during transfer of immune complexes and pathogens from RBC to macrophages

NAD(P)H:quinone oxidoreductase 1 inducer activity of some novel anilinoquinazoline derivatives

The Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements pathway enables cells to survive oxidative stress conditions through regulating the expression of cytoprotective enzymes such as NAD(P)H:quinone oxidoreductase 1 (NQO1). This work presents the design and synthesis of novel anilinoquinazoline derivatives (2–16a) and evaluation of their NQO1 inducer activity in murine cells. Molecular docking of the new compounds was performed to assess their ability to inhibit Keap1–Nrf2 protein–protein interaction through occupying the Keap1–Nrf2-binding domain, which leads to Nrf2 accumulation and enhanced gene expression of NQO1. Docking results showed that all compounds can potentially interact with Keap1; however, 1,5-dimethyl-2-phenyl-4-(2-phenylquinazolin-4-ylamino)-1,2-dihydropyrazol-3-one (9), the most potent inducer, showed the largest number of interactions with key amino acids in the binding pocket (Arg483, Tyr525, and Phe478) compared to the native ligand or any other compound in this series